Continued support is sought for a multifaceted study of human and experimental muscle diseases with light, phase and electron microscopy, electron microscopic cytochemistry, immuno-electron microscopy, tissue culture methods, freeze-fracture electron microscopy and correlated biochemical and electrophysiologic investigations. Ultrastructural reactions of the muscle fiber organelles and of the neuromuscular junction will be investigated and quantitated by morphometric methods. Myasthenia gravis and its experimental autoimmune model will be analyzed to establish the relative importance of immunopathologic mechanisms which result in a deficiency of the acetylcholine receptor protein. The interactions between acetylcholine receptor, antibody and complement ccmponents, the pathogenesis of the destructive changes at the end-plate and the mechanisms of impaired neuromuscular transmission will be analyzed. The ultrastructural and biochemical studies will be carried out in a newly recognized congenital myasthenic syndrome. In Duchenne dystrophy the plasma membrane of cultured muscle fibers will be studied by freeze-fracture electron microscopy for expression of the muscle plasma membrane abnomalities which have been observed in patients.